Noninvasive monitoring of red blood cell transfusion in very low birthweight infants using diffuse optical spectroscopy.

Red blood cell (RBC) transfusion guidelines are designed to maintain adequate tissue oxygenation by increasing blood oxygen-carrying capacity. However, since tissue oxygenation is not measured, RBC transfusion guidelines are mostly subjective. Clinical evidence of oxygen transport/consumption mismatches in infants is often unclear and confounded by multiple factors. Invasive hemoglobin measurements can contribute further to anemia if performed too frequently. Diffuse optical spectroscopy (DOS) is a noninvasive quantitative method to measure the tissue oxy, deoxy, and total hemoglobin concentrations (ctO2Hb, ctHb, ctTHb), as well as mixed arterial-venous tissue hemoglobin saturation (stO2). Our objective is to determine if DOS can assess changes in tissue oxygenation in very low birth weight (VLBW) infants undergoing RBC transfusions. DOS measurements of ctO2Hb and ctHb are performed on 10 VLBW infants before and within 24 h after RBC transfusion. Seven nontransfused infants are studied to evaluate hemodynamic variations independent of RBC transfusion. Tissue near-infrared absorption and scattering values are measured using a four-wavelength (690, 750, 810, and 830 nm) frequency-domain tissue oximeter (OxiplexTS, ISS, Champaign, Illinois). In transfused subjects, DOS demonstrates significant increases in ctO2Hb (48+/-13 versus 74+/-20 microM, p<0.002), ctTHb (87+/-17 versus 107+/-24 microM, p=0.004), and stO2 (54+/-8 versus 68+/-6%, p<0.004) post-transfusion. DOS measurements correlate with mean hemoglobin increases for all infants (r=0.83, p<0.0001). No significant DOS changes occurred in the nontransfused group. Calculations of the differential path length for these transfused subjects show high variability (approximately 20%). DOS may serve as a noninvasive bedside tool to assess tissue oxygenation in infants and provide a functionally based transfusion trigger.

Influence of morphine and naloxone on endothelin and its receptors in newborn piglet brain vascular endothelial cells: clinical implications in neonatal care.

The present study examines the hypothesis that morphine exposure alters newborn brain vascular endothelial cell production of endothelin (ET)-1, as well as the mRNA expression of its receptors. Newborn piglet vascular endothelial cells were treated with morphine (100 ng/mL media), naloxone (100 ng/mL media), or drug-free media (control) for 6, 24, 48, and 96 h. Media was analyzed for ET-1 and big ET-1 levels and the cells were assessed for ETA and ETB receptor mRNA expression. Morphine exposure progressively increased ET-1 production from 6 to 96 h with concurrent reductions in big ET-1 levels starting at 24 h to almost undetectable levels by 96 h. Whereas ETA receptor mRNA expression increased 2-fold at 6 h and 4-fold at 96 h, ETB receptor mRNA expression remained unchanged. Naloxone exposure caused significant decreases in ET-1 levels, whereas an opposite effect was noted in big ET-1 levels, which increased from 6 through 96 h. Naloxone caused a progressive decrease in ETA receptor mRNA expression at 6 h through 96 h and a 2-fold increase in ETB receptor mRNA expression at 48 and 96 h. Increased ET-1 and its receptors in response to morphine may suggest altered cerebrovascular perfusion and brain metabolism in the immature piglet brain.

Early postnatal dexamethasone influences matrix metalloproteinase-2 and -9, and their tissue inhibitors in the developing rat lung.

In order to test the hypothesis that early postnatal exposure to dexamethasone (Dex) influences matrix metalloproteinases (MMP)-2 and -9, as well as their tissue inhibitors (TIMP-1 and -2) in the developing rat lung, newborn rats (3 litters/group) were treated with low Dex (0.1 mg/kg/day, IM), high Dex (0.5 mg/kg/day), or equivalent volumes of saline at 5 days postnatal age (P5), P6, and P7. Lung weight and lung MMP and TIMP levels were determined at sacrifice (7 days postinjection, P14; at weaning, P21; and at adolescence, P45, n = 10/group and time). Dex did not adversely affect lung weight or lung MMP-2 levels, which peaked in all groups at P21 and then fell by P45. In contrast, Dex decreased TIMP-2 at all time intervals, but achieved statistical significance only at P45. An imbalance in MMP-2/TIMP-2 ratio was noted at P21, with elevations occurring in the low and high Dex-treated groups. Lung MMP-9 levels remained comparable with controls during low Dex treatment. However, high Dex exposure resulted in elevated lung MMP-9 levels at P21 and P45. Lung TIMP-1 levels increased only with high Dex exposure at P14 and P21, whereas the lung MMP-9/TIMP-1 ratio was elevated at P21 in the high Dex group, and at P45 in both Dex-treated groups. These data provide evidence that early postnatal dexamethasone results in an imbalance between gelatinase-A and -B, and their tissue inhibitors in the developing rat lung. These changes may be responsible, in part, for some of the known maturational effects of steroids on lung structure in the newborn.